Clinical hypo- and hypercalcemia are frequently accompanied by disturbed function of the central nervous system, usually attributed to abnormal cerebral interstitial calcium activity. In apparent contradiction to this view, published laboratory reports emphasize the independence of ion activities in both cerebrospinal fluid and in cerebral interstitial fluid from that in circulating blood. The project proposed here is designed to resolve this conflict and it has two major goals: A. To determine the degree to which cerebral interstitial calcium activity depends on plasma ionized and total calcium, and on plasma and cerebral pH. B. To determine the effect of altered cerebral tissue calcium activity on cerebral function. To achieve these goals acute and chronic changes of calcium activity levels will be induced. The effects of respiratory and metabolic alkalosis on calcium activity in blood and in cerebral tissue and on neuronal function will also be observed. Further, the interactions of altered calcium, magnesium, pH and pO2 levels on neuronal function will be evaluated. Ionized calcium activity and pH will be measured in circulating arterial blood and in cerebral interstitial space with ionselective electrodes. Oxygen tension will be measured polarographically with a microelectrode. In addition, total Ca, Mg, pH, pO2, and, in some experiments, parathormone levels, will be measured in samples of arterial blood. Neuronal functions, including EEG, seizure threshold, evoked potentials, excitatory and inhibitory synaptic functions, neuronal membrane properties will be assessed in intact brain and spinal cord and in cerebral tissue slices maintained in vitro.